chr5-41196973-A-G

Variant names:

• chr5-41196973-A-G
• rs13168926
• NM_000065.5:c.446-1040T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000065.5(C6):​c.446-1040T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.531 in 151,892 control chromosomes in the GnomAD database, including 21,904 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.53 (21904 hom., cov: 31)
• Consequence: C6 NM_000065.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0750
• Publications: 4 publications found

Genes affected

C6 (HGNC:1339): (complement C6) This gene encodes a component of the complement cascade. The encoded protein is part of the membrane attack complex that can be incorporated into the cell membrane and cause cell lysis. Mutations in this gene are associated with complement component-6 deficiency. Transcript variants encoding the same protein have been described.[provided by RefSeq, Nov 2012]

C6 Gene-Disease associations (from GenCC):

• complement component 6 deficiency

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.595 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
C6	NM_000065.5	c.446-1040T>C		intron_variant	Intron 4 of 17	ENST00000337836.10	NP_000056.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
C6	ENST00000337836.10	c.446-1040T>C		intron_variant	Intron 4 of 17	1	NM_000065.5	ENSP00000338861.5

Frequencies

GnomAD3 genomes AF: 0.532 AC: 80689 AN: 151774 Hom.: 21909 Cov.: 31

Gnomad AFR AF: 0.418

Gnomad AMI AF: 0.470

Gnomad AMR AF: 0.539

Gnomad ASJ AF: 0.532

Gnomad EAS AF: 0.436

Gnomad SAS AF: 0.575

Gnomad FIN AF: 0.555

Gnomad MID AF: 0.475

Gnomad NFE AF: 0.600

Gnomad OTH AF: 0.550

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.531 AC: 80702 AN: 151892 Hom.: 21904 Cov.: 31 AF XY: 0.530 AC XY: 39385 AN XY: 74258

African (AFR) AF: 0.417 AC: 17280 AN: 41450

American (AMR) AF: 0.539 AC: 8207 AN: 15226

Ashkenazi Jewish (ASJ) AF: 0.532 AC: 1842 AN: 3460

East Asian (EAS) AF: 0.436 AC: 2248 AN: 5158

South Asian (SAS) AF: 0.575 AC: 2769 AN: 4814

European-Finnish (FIN) AF: 0.555 AC: 5856 AN: 10548

Middle Eastern (MID) AF: 0.466 AC: 137 AN: 294

European-Non Finnish (NFE) AF: 0.600 AC: 40771 AN: 67922

Other (OTH) AF: 0.552 AC: 1163 AN: 2108

Alfa AF: 0.562 Hom.: 32565

Bravo AF: 0.520

Asia WGS AF: 0.502 AC: 1741 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.95
DANN	Benign	0.42
PhyloP100		0.075
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs13168926; hg19: chr5-41197075;